|Ahead of print publication
Dosimetric comparison of modern radiotherapy techniques for gastric cancer after total gastrectomy
Pelin Altinok1, Ertugrul Tekçe1, Fatih Karaköse1, Kemal Berk1, Ümmühan Kalafat2, Huriye Senay Kiziltan1, Züleyha Akgün2, Alpaslan Mayadagli1
1 Department of Radiation Oncology, Bezmialem Vakif University, Istanbul, Turkey
2 Department of Radiation Oncology, Memorial Hospital Sisli, Istanbul, Turkey
Department of Radiation Oncology, Bezmialem Vakif University, Adnan Menderes Bulvari, Fatih, Istanbul
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of this study is to investigate the optimal radiotherapy technique for postoperative irradiation of gastric cancer treated with total gastrectomy.
Materials and Methods: The database of ten patients was used for this study. Three-dimensional (3D) conformal radiotherapy, intensity-modulated therapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) plans were created for each dataset. The prescription dose was 45 Gy in 25 fractions. Comparative analyses of the target volume coverage and the doses of organs at risk were performed.
Results: HT was significantly provided more homogeneity. The best conformal plans were achieved with VMAT. Both kidneys were better preserved with HT and VMAT. HT significantly lowered the V13 of the left kidney and VMAT significantly lowered V20. However, the mean left kidney doses were not statistically different. The lowest liver V30 was obtained with VMAT but not with statistically different than IMRT and HT. Mean liver doses were statistically inferior with 3D. The worst spinal cord doses were seen with 3D. The integral dose of the body did not differ among the techniques.
Conclusion: In comparison of the four techniques, 3D seems to be the most unsuitable method regarding sparing the normal tissues. According to availability, HT and VMAT should be primarily preferred. IMRT can also be used with carefully paying attention to the clinical condition of the patient.
Keywords: Gastric cancer, helical tomotherapy, intensity-modulated therapy, three-dimensional conformal radiotherapy, volumetric modulated arc therapy
|How to cite this URL:|
Altinok P, Tekçe E, Karaköse F, Berk K, Kalafat &, Kiziltan HS, Akgün Z, Mayadagli A. Dosimetric comparison of modern radiotherapy techniques for gastric cancer after total gastrectomy. J Can Res Ther [Epub ahead of print] [cited 2020 Feb 28]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=270099
| > Introduction|| |
Gastric cancer is still one of the common cause of cancer-related deaths worldwide., Adjuvant chemoradiation became the standard of care for high-risk patients after INT-0116 trial. Although this approach prolongs survival and reduces the local recurrence rates, toxicity due to the therapy is a remaining issue.
Regarding radiotherapy technique, three-dimensional (3D) radiotherapy was found to be superior to two-dimensional (2-D) treatment planning. Further studies showed that intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have better coverage of planning target volume (PTV) and also a better normal tissue sparing.,,,
We investigated the best compatible radiotherapy technique comparing 3D, IMRT, VMAT, and helical tomotherapy (HT) for adjuvant treatment of gastric cancer with this study.
| > Materials and Methods|| |
Patients and volume definition
Institutional Ethics Board approval was obtained. Ten patients were selected for this study. All patients had total gastrectomy for fundus-corpus-antrum-located tumors. All had negative surgical margins with T4aN2-3 disease. This selection was made to achieve the possible largest treatment fields. Computed tomography (CT) scans which were generated for radiotherapy planning were used. After fasting for 3–4 h, the patients were immobilized in a supine position on a T-board with arms raised above the head. No intravenous contrast was administered if the patient had a CT with contrast before the surgery. The slice thickness was 3 mm. Free breathing was performed.
The target volumes and organs at risk (OAR) were contoured on axial slices by the same radiation oncologist. To define the volumes, individual patient data of presurgical CT (with a generated deformable fusion on treatment planning system [TPS]), endoscopic, and pathological findings were used. The clinical target volume (CTV) included the tumor bed, anastomoses, and the draining lymph node stations (perigastric, celiac, splenic, peripancreatic, paraaortic, and hepatoduodenal). For the delineation of lymph node stations, the gastric lymph node atlases of Massachusetts General Hospital  and Zhongnan Hospital of Wuhan University  and recommendations of Gunderson and Tepper  as well as International Commission on Radiation Units and Measurements reports 50 and 62 were taken into account. PTV was constructed by a 1-cm margin to the CTV. Kidneys, liver, and spinal cord were defined as OAR.
For 3D and IMRT plans and VMAT plans, Varian Clinac DHX linear accelerator and Varian Truebeam linear accelerator were used (Varian Medical Systems, Palo Alto, CA, USA), respectively. The plans were generated on Eclipse TPS.
Field-in-field (FIF) technique was applied for the 3D plans. There were five FIF fields at the angles 0, 90 and 270. The photon beam energy was 18 MV. IMRT had inversely planned seven coplanar fields at the angles of 150°, 100°, 50°, 0°, 310°, 260°, and 210° with 6 MV photon beams. VMAT plans were generated with two full coplanar arcs at 179°–181° and reversed with a collimator angle at 30°. The photon beam energy was 10 MV.
HT plans were created with the superposition-convolution system method on the VoLO TPS (Accuray Incorporated, Sunnyvale, CA, USA). Helical IMRT technique was applied with HT-HDA with a photon beam energy of 6 MV.
The prescribed dose was 45 Gy in 25 fractions. The main aim of all the plans was to cover the PTV. The optimization of the plans was done as the PTV coverage to be between 98% and 108% of the prescribed dose. Inhomogeneity corrections were applied during treatment planning. Dose constraints for OAR were as follows: maximum spinal cord dose (Dmax) <45 Gy, mean liver dose (Dmean) <32 Gy, and liver volume receiving 30 Gy (V30) <30%. Mean kidney dose <18 Gy, V13, and V20 for the kidneys <50% and <70%, respectively. Body volumes receiving doses 5 Gy (V5) and 20 Gy (V20) were reviewed as integral doses but were not taken into account as constraints.
Dose-volume histograms were generated for all plans. Conformity indexes (CIs) and homogeneity indexes (HIs) were calculated for each plan. CI = (PTV∩95%)2/(PTVv× 95%v). This ratio is preferred to take into account the volume of overlap between the structures. The ideal value for perfect conformity is 1. HI = (D2% − D98%/D50%) where D98 and D2 were the dose values covering 98% and 2% of the PTV, respectively, and D50 was the median dose. The smaller values closer to 0 indicate superior homogeneity. The planning parameters of OARs for each patient were also analyzed as follows: Dmax to the spinal cord, mean liver and kidney doses, V30 of the liver, and V13 and V20 for the kidneys [Figure 1].
|Figure 1: Dose distributions of the same patient in axial, coronal, and sagittal views with three-dimensional (a), intensity-modulated radiation therapy (b), volumetric modulated arc therapy (c), and helical tomotherapy (d) plans 95% coverage of the prescribed dose of each plan is presented|
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Data were analyzed using SPSS software version 20 (SPSS, Inc., Chicago, IL, USA). ANOVA and Tukey's multiple comparison tests were performed. However, as HI found to be nonnormalized on One-sample Kolmogorov–Smirnov test, nonparametric Kruskal–Wallis test was applied for HI to search a significant difference, if any. The statistical significance level was considered as P < 0.05.
| > Results|| |
The plans of VMAT had the best conformity (P < 0.001); however, HT and IMRT also provided sufficient results (mean CI was 0.89 ± 0.02 for IMRT and 0.72 ± 0.23 for HT). HT was significantly better than both IMRT and VMAT regarding homogeneity (P = 0.005). Median HI for HT was 0.06 whereas it was 0.1 for IMRT and 0.07 for VMAT. Less suitable results of CI and HI were seen with 3D plans (CI Mean 0.57 ± 0.04 and HI median 0.1).
Spinal cord doses were significantly higher in 3D plans where the doses of other techniques were similar (P = 0.04).
The right kidney was significantly better preserved with HT and VMAT. Both mean, V13, and V20 values were lower than 3D and IMRT (mean dose P = 0.02, V13 P < 0.001 and V20 P < 0.001).
HT and VMAT were significantly lowered the V13 and V20 doses of the left kidney (P = 0.001 and P = 0.04, respectively). Lowest V13 doses were seen with HT (mean 31.78 ± 11.94), and lowest V20 doses were obtained with VMAT (mean 17.95 ± 5.05). However, the mean doses were similar among the four methods.
Mean liver doses were significantly lower with both IMRT, HT and VMAT (P < 0.001). The same significance was achieved for V30 of the liver (P < 0.001). VMAT plans assured the lowest V30 dose (mean 21.82 ± 4.31).
The integral doses of the body which could be defined with V5 and V20 did not significantly differ among the techniques (P = 0.7 and P = 0.06, respectively).
The results and the value of significance are summarized in [Table 1].
| > Discussion|| |
Central location in the abdomen and extensive lymphatic drainage of the stomach cause a relatively wide irradiation field. This handicaps the effective protection of the surrounding normal tissues, especially the liver and the kidneys. The most appropriate technique for postgastrectomy radiotherapy is still under research.
Early studies comparing traditional 2D approach with 3D showed some conflicting results regarding sparing OAR. High liver and left kidney doses enforced the researchers to find better solutions with the newer irradiation techniques such as IMRT, VMAT, and HT.
Lohr et al. compared 8-field step-and-shoot IMRT and 3D and found that the liver and the left kidney were significantly better preserved with IMRT. Spinal cord doses were higher but not statistically significant. Milano et al. produced similar results for the liver and the kidneys. Murthy et al. evaluated if there is any difference between IMRT and the two arrangements of 3D plans. The 3-field and 4-field 3D plans did not differ from each other and IMRT was significantly better just regarding mean liver doses. From the opposite point of view, Ma et al. compared two different IMRT plans with 3D. Particularly, maximum spinal cord and mean liver doses were improved with IMRT. However, the mean doses of the kidneys in both 5- and 7-field IMRT plans were higher. As a contrary result, Serarslan et al. found significantly better kidney doses using both FIF and dynamic IMRT techniques comparable to 3D. The mean doses and V30 of the liver were also better with IMRT; however, dynamic IMRT was the worst technique to spare the spinal cord. Yet, Alani et al. stated higher liver doses with 9-field IMRT whereas significantly better kidney and marginally better spinal cord doses. Apart from the dosimetric studies, Minn et al. presented their clinical data showing that in long-term follow-up, the reduced V20 doses of the kidneys reflected better creatinine levels with IMRT rather than 3D plans. In the current study, comparing 3D and IMRT, CI was statistically better with IMRT plans. HI was not different. Highest spinal cord doses were seen with 3D but not statistically different than IMRT. This can be explained by that both plans did not use a posterior field. Furthermore, the spinal cord was covered with a FIF technique in 3D plans. Liver mean and V30 doses were statistically better with IMRT. Both kidney means, V13 and V20 doses, did not demonstrated a significance, yet right kidney V20 was slightly better in IMRT plans. As we used a 7-field IMRT, this may resulted in a lower spinal cord but higher kidney doses.
VMAT both with single-arc (SA) and double-arc (DA) was also questioned in several studies. Wang et al. showed no significant difference between SA-VMAT and IMRT other than liver V20, which was better with SA-VMAT. The 3D technique was only better for the spinal cord. By utilizing DA-VMAT plans, Zang et al. obtained significantly lower spinal cord, liver V30, and kidney V20 doses. There was no difference between the mean doses. Li et al. investigated for the best method using two different IMRT and VMAT techniques. Among these four (5-field IMRT, 7-field IMRT, SA-VMAT, and DA-VMAT), DA-VMAT achieved the best CI, HI, and also significantly lower kidney mean, V13, and V18 doses. Mean liver doses were lowest with 5-field IMRT, and liver V30 was higher with SA-VMAT. In this study, VMAT did not provide better spinal cord protection than IMRT. Although mean kidney doses were not statistically different among 3D, VMAT, and IMRT, the significance was observed in favor of VMAT for the right kidney V13 (better than both) and V20 (better than 3D). Furthermore, the left kidney V13 was better than IMRT and V20 was better than 3D and were statistically significant. The liver mean and V30 were significantly better than 3D but similar to IMRT. Regarding lowering the V20 of both kidneys, VMAT and IMRT provided similar results.
In an early study conducted by Dahele et al., HT had superior HI but gave the same results with IMRT regarding OAR. More recent studies worked on comparing newer HT equipment. Wang et al. found that HT had significantly better CI and HI than IMRT and SA-VMAT. Liver V5 and V40 doses were significantly better with HT plans; however, SA-VMAT was superior for V20 of the left kidney. In a newer study, Önal et al. compared HT with DA-VMAT and 3D. HT was found to be significantly better for CI, mean liver, and kidney doses, as well as liver V20 and V30. HT and DA-VMAT were similar and significantly better than 3D for V20 of the kidney. In the current study, HT plans had significantly better HI than IMRT and VMAT plans. However, we did not reach any significant level between HT and VMAT regarding kidney and liver sparing. Probably, the wide treatment fields used in this study are the reason for these results.
Although all treatment plans have been optimized to a clinical treatment standard, current is a dosimetric study and cannot reflect the real clinical impacts completely and also has limitations with smaller sample size.
| > Conclusion|| |
As a summary of the studies which are perplexing ever and anon, it is obviously clear that the actual techniques achieve better PTV coverage and preserve OAR better than 3D. In most studies, in comparison with IMRT, liver and kidneys are better protected with HT and VMAT. Further dosimetric studies are expected to include respiratory motion parameters. This approach will probably lower the doses of both kidneys and the liver.
The study conforms to be compatible with the principles outlined in Helsinki Declaration.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
World Health Organization. Cancer Country Profiles. World Health Organization; 2014. Available from: https://www.who.int/cancer/en/
. [Last access on 2019 Apr 25].
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al.
Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30.
Ringash J, Khaksart SJ, Oza A, Couture J, Japp B, Moore M, et al.
Post-operative radiochemotherapy for gastric cancer: Adoption and adaptation. Clin Oncol (R Coll Radiol) 2005;17:91-5.
Alani S, Soyfer V, Strauss N, Schifter D, Corn BW. Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer. Int J Radiat Oncol Biol Phys 2009;74:562-6.
Minn AY, Hsu A, La T, Kunz P, Fisher GA, Ford JM, et al.
Comparison of intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer 2010;116:3943-52.
Dahele M, Skinner M, Schultz B, Cardoso M, Bell C, Ung YC, et al.
Adjuvant radiotherapy for gastric cancer: A dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapy and conventional intensity modulated radiotherapy treatment plans. Med Dosim 2010;35:115-21.
Li Z, Zeng J, Wang Z, Zhu H, Wei Y. Dosimetric comparison of intensity modulated and volumetric arc radiation therapy for gastric cancer. Oncol Lett 2014;8:1427-34.
Wo JY, Yoon SS, Guimaraes AR, Wolfgang J, Mamon HJ, Hong TS, et al.
Gastric lymph node contouring atlas: A tool to aid in clinical target volume definition in 3-dimensional treatment planning for gastric cancer. Pract Radiat Oncol 2013;3:e11-9.
Haijun Y, Qiuji W, Zhenming F, Yong H, Zhengkai L, Conghua X, et al.
A new approach to delineating lymph node target volumes for post-operative radiotherapy in gastric cancer: A phase II trial. Radiother Oncol 2015;116:245-51.
Gunderson LL, Tepper JE, Calvo FA, Ashman JB. Gastric/GE junction cancer. In: Gunderson LL, Tepper JE, editors. Clinical Radiation Oncology. 4th
ed. Philadelphia: Elsevier; 2016. p. 906-33.
Paddick I. A simple scoring ratio to index the conformity of radiosurgical treatment plans. Technical note. J Neurosurg 2000;93 Suppl 3:219-22.
Morganti AG, Di Castelnuovo A, Massaccesi M, Cellini F, Cilla S, Macchia G, et al.
Planning comparison between standard and conformal 3D techniques in post-operative radiotherapy of gastric cancer: A systematic review. Br J Radiol 2013;86:20130274.
Lohr F, Dobler B, Mai S, Hermann B, Tiefenbacher U, Wieland P, et al.
Optimization of dose distributions for adjuvant locoregional radiotherapy of gastric cancer by IMRT. Strahlenther Onkol 2003;179:557-63.
Milano MT, Garofalo MC, Chmura SJ, Farrey K, Rash C, Heimann R, et al.
Intensity-modulated radiation therapy in the treatment of gastric cancer: Early clinical outcome and dosimetric comparison with conventional techniques. Br J Radiol 2006;79:497-503.
Murthy K, Shukeili K, Kumar S, Davis C, Chandran R, Namrata S, et al.
Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT. Biomed Imaging Interv J 2010;6:e29.
Ma H, Han J, Zhang T, Ke Y. Comparison of dosiology between three dimensional conformal and intensity-modulated radiotherapies (5 and 7 fields) in gastric cancer post-surgery. J Huazhong Univ Sci Technolog Med Sci 2013;33:759-64.
Serarslan A, Ozbek Okumus N, Gursel B, Meydan D, Dastan Y, Aksu T, et al.
Dosimetric comparison of three different radiotherapy techniques in antrum-located stomach cancer Asian Pac J Cancer Prev 2017;18:741-6.
Wang X, Li G, Zhang Y, Bai S, Xu F, Wei Y, et al.
Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). Med Dosim 2013;38:395-400.
Zhang T, Liang ZW, Han J, Bi JP, Yang ZY, Ma H, et al.
Double-arc volumetric modulated therapy improves dose distribution compared to static gantry IMRT and 3D conformal radiotherapy for adjuvant therapy of gastric cancer. Radiat Oncol 2015;10:114.
Wang X, Tian Y, Tang Y, Hu ZH, Zhang JJ, Fu GS, et al.
Tomotherapy as an adjuvant treatment for gastroesophageal junction and stomach cancer may reduce bowel and bone marrow toxicity compared to intensity-modulated radiotherapy and volumetric-modulated arc therapy. Oncotarget 2017;8:39727-35.
Onal C, Dölek Y, Akkuş Yıldırım B. Dosimetric comparison of 3-dimensional conformal radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for postoperative gastric cancer patients. Jpn J Radiol 2018;36:30-9.